Physical biochemical studies of complex protein-protein and protein-membrane interactions are proposed. Specific attention will focus on interactions of blood coagulation, with emphasis on the conversion of prothrombin to thrombin. Binding of factor V, factor Xa and prothrombin to each other and to phospholipid vesicles will be measured and correlated with kinetics of the prothrombinase reaction. The objective is to understand the kinetic properties of thrombin generation and the role of membrane in rate enhancement. Major physical methods to be used include light scattering, quasi-elastic light scattering and fluorescence. These methods measure different parameters and consequently they can be used to crosscheck and corroborate each other. Binding of proteins (e.g., thrombin and antithrombin III) to heparin is another example of interaction of different classes of biochemicals. These interactions will be investigated to determine binding constants and the number of sites per unit length of the heparin molecule. As the investigation proceeds these physical techniques may provide new approaches to assessing heparin function. Finally, we propose to study other protein-membrane interactions, beginning with S-100 protein of nervous tissue and cholera toxin.